Hypogeusia

A Case Report

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The diagnosis came from a non-medical book:

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“Remove zinc from your diet and you will get a condition known as hypogeusia, in which your taste buds stop working, making food boring or even revolting, but until as recently as 1977 zinc was thought to have no role in diet at all.” The quote leaped from the page of a book “At Home” by Bill Bryson.

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Food aversion. Revulsion toward food.

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Hypogeusia is a diminished sense of taste resulting from zinc deficiency. The patient slowly, week after week, developed a severe aversion to all food groups except cappuccino (arginine).

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Month after month it became severe before the patient was finally able to identify a descriptive term “food aversion.” Hunger was severe. Patient was desperate to find fuel for body that was not revolting.

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Not anorexia – means loss of appetite. The patient was starving.

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Not anorexia nervosa – a distorted body image in which patients severely restrict food intake and can starve to death.

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Not depression – depressed mood often associated with poor appetite or stress eating.

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Food aversion was bizarre, going to bed starving while the best foods were sitting in the fridge untouched and literally repulsive even to think about. For months, walking up and down grocery aisles, repulsed by the thought of the finest foods despite hunger, craving to find some form of fuel that was not revolting. Months and months went by as it became severe. Past favorite foods might as well have been poison. Flavor was wanting.

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Specialists and literature searches commonly view food aversion as psychosomatic or the bizarre cravings of pregnancy. Females are at particular risk of being assigned psychological diagnoses. We do our patients a disservice failing to appreciate the complexity of human physiology with our limited understanding of evolving science. The human body is complex.

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To complicate matters, it’s not easy to diagnose depression – not all patients recognize it in themselves. Further, zinc deficiency induces depressive behaviors, plays a major role in major depressive disorder and is a risk factor for treatment resistance — referenced below at end.

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Aversion became extreme before the patient could name the correct term: food aversion, no doubt why it is barely mentioned in medical searches: a condition must have a name before it can exist, before it can be identified and understood as a symptom. Hunger at times was severe, but just the thought of driving to the grocery store was troubling and wasted hours. Complicating the picture, the coexisting autoimmune disorder also caused anorexia, i.e. loss of appetite.

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Then that sentence leaped from the page naming the cause: Zinc deficiency. What causes zinc deficiency? Malnutrition, medications. You have to string together the right words in order to search the publication leads. Thus, when you specifically search food aversion and prednisone:

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“Food aversion is found among people who take Prednisone, especially for people who are female, 60+ old , have been taking the drug for 1 – 6 months, also take medication Methotrexate, and have Osteoporosis.”

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The patient stopped methotrexate. Six weeks went by before a small number of foods could be added to milk and eggs. Unfortunately, the only foods tolerated were easily digestible ice cream (protein), pasta and sweets, which leads me to recall patients with autoimmune disorders whose diet consisted of processed carbs such as English Muffins, bread, pasta, who complain they cannot eat anything yet they are obese. They cannot seem to change food choices. How many cancer patients have this problem from chemotherapy?

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Vegetarians are at risk of zinc deficiency since Zinc is available primarily in oysters, meat, and poultry. Among the many causes of gustatory (taste) dysfunction in Table 6 from 2013 American Family Physician, besides malnutrition are cancer, radiation, etc, a long list of medications are listed:

Chemotherapy, statins, antidepressants, blood pressure medications, antibiotics – many commonly used medications can cause deficiency, yet zinc deficiency is said to be rare. Are we failing to recognize this in our patients?

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If dysfunction occurs, stop the offending medication. Regarding chemotherapy, “These effects are usually transient and resolve within three months of treatment cessation. This adverse effect is most likely caused by toxicity to olfactory and gustatory receptor cells that have the ability to regenerate.”

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“Zinc is involved in numerous aspects of cellular metabolism. It is required for the catalytic activity of approximately 100 enzymes [1,2] and it plays a role in immune function [3,4], protein synthesis [4], wound healing [5], DNA synthesis [2,4], and cell division [4]. Zinc also supports normal growth and development during pregnancy, childhood, and adolescence [6-8] and is required for proper sense of taste and smell [9]. A daily intake of zinc is required to maintain a steady state because the body has no specialized zinc storage system [10].”

Serum levels of zinc and copper can be tested but do not reflect levels in the body as they are stored in tissue.

“The ratio of copper to zinc is clinically more important than the concentration of either of these trace metals. Zn is the second most abundant transition metal in organisms after iron and it is the only metal which appears in all enzyme classes, while copper is present in every tissue of the body, but is stored primarily in the liver, with fewer amounts found in the brain, heart, kidney, and muscles.”

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…The optimal plasma or serum ratio between these two elements is 0.70 – 1.00 [1]….

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“There are 2-4 grams of Zn distributed throughout the human body [2]. Most zinc is in the brain [primarily hippocampus, the limbic system], muscle, bones, kidney and liver, with the highest concentrations in the prostate and parts of the eye [3]. It is the second most abundant transition metal in organisms after iron and it is the only metal which appears in all enzyme classes [2,4].

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Copper is also a vital dietary nutrient, although only small amounts of the metal are needed for well-being [5]. Although copper is the third most abundant trace metal in the body [behind iron and zinc], the total amount of copper in the body is only 75-100 milligrams [6]. Copper is present in every tissue of the body, but is stored primarily in the liver, with fewer amounts found in the brain, heart, kidney, and muscles [7]….

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Diagnosing zinc deficiency is a persistent challenge. Zinc nutritional status is difficult to measure adequately using laboratory tests due to its distribution throughout the body as a component of various proteins and nucleic acids [18,136].”

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Plasma or serum zinc has “poor sensitivity and specificity – these levels do not necessarily reflect cellular zinc status due to tight homeostatic control mechanisms.”

“Since plant sources of zinc contain phytate and other inhibitors of zinc absorption, vegetarians and vegans may potentially be at risk of zinc deficiency.”

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Special cases such as those with inflammatory bowel disease, those with profuse diarrhea, or who have had bariatric surgery should consult with a nutritionist.

Zinc Therapy in Dermatology: A Reviewfrom 2014 is an open access PDF. Zinc is discussed in various conditions including eczema, psoriasis & psoriatic arthritis, acne, alopecia, seborrheic dermatitis, dandruff, etc.

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“It maintains macrophage and neutrophil functions, natural killer cell activity, and complement activity. It activates natural killer cells and phagocytic function of granulocytes and stabilizes the plasma subcellular membranes especially the lysosomes. It inhibits the expression of integrins by keratinocytes and modulates the production of TNF-𝛼 and IL-6 and reduces the production of inflammatory mediators like nitric oxide. It is also proposed that it is toll-like receptors mediated regulation of zinc homeostasis which influences dendritic cell function and immune processes [2]. Zinc also possesses antioxidant property and has been found useful in preventing UV- induced damage and reducing the incidence of malignancies. It has also been demonstrated to possess antiandrogenic properties as it causes modulation of 5𝛼-reductase type 1 and 2 activity [1, 3, 4].”

Based on limited reading, for zinc deficiency – NOT routine use – consider 20 to 50 mg zinc with 2 mg copper for a limited time. Follow cautiously for toxicity. HIGH AMOUNTS OF ZINC ARE UNSAFE.

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Available Forms

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Zinc is available in several forms….

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More easily absorbed forms of zinc are zinc picolinate, zinc citrate, zinc acetate, zinc glycerate, and zinc monomethionine. If zinc sulfate causes stomach irritation, you can try another form, such as zinc citrate.

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The amount of elemental zinc is listed on the product label (usually 30 – 50 mg). To determine the amount to take in supplement form, remember that you get about 10 – 15 mg from food. [if you eat oysters, meat, poultry]

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Zinc lozenges, used for treating colds, are available in most drug stores. There are also nasal sprays developed to reduce nasal and sinus congestion, although they may have some safety issues (see “Precautions”). [Avoid nasal sprays as it destroys the olfactory nerve, the sense of smell.]

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How to Take It

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You should take zinc with water or juice. If zinc causes stomach upset, it can be taken with meals. Don’t take zinc at the same time as iron or calcium supplements.

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A strong relationship exists between zinc and copper. Too much of one can cause a deficiency in the other.If you take zinc, including zinc in a multivitamin, you should also take copper..

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Take copper on an empty stomach. The tablets I have seen are so tiny they stick in the throat. Copper is water soluble but dissolves better in hot water.

“Consumption of zinc >100 mg/day may increase the risk of prostate cancer (31).

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Although human studies have been equivocal, patients should take zinc 2 hours before or after foods that are high in calcium, phosphorus, bran fiber, or phytate to avoid nonabsorbable complexes (45)(67).

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When taken orally at large doses (100-300 mg/day),zinc can cause chronic toxicity including copper deficiency, depressed immune function, headache, chills, fever, and fatigue(58)(59).”

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“Intake recommendations for Zn are provided in the Dietary Reference Intakes developed by the Food and Nutrition Board (FNB) at the Institute of Medicine of the National Academies…. U.S. National Research Council set a Tolerable Upper Intake for adults of 40 mg/day[82,83].

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Recommended daily allowance for Zn

RDAs 8 mg/day for female, 11 mg/day for male

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Recommended intake for copper

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The 10th edition of Recommended Dietary Allowances (RDA) did not include an RDA for copper; rather a safe and adequate daily intake was suggested…. The following Table 2 provide the Recommended daily dietary intake (RDI) of copper for children and adults and Tolerable upper intake levels for copper [83,85].

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Recommended daily intake RDI’s

90 mcg

Tolerable upper intake levels TUL10,000 mcg”

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Of interest, a 2005 publication, Re-establishment of olfactory and taste functions describes results of treatment. Very small numbers were tested limiting interpretation. Were large doses complicating the results, causing toxicity and/or copper deficiency?

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In an open study (n=119; idiopathic taste disturbance, n=45; drug-induced taste disturbance, n=38; zinc deficiency, n=36), taste improvement by 50% was achieved after 4 weeks and by 80% after 8 weeks of treatment with zinc sulfate (100 mg, three times daily) [201]. In a double-blind, placebo-controlled study (n=73; idiopathic taste disturbance, n=48; lowered zinc levels, n=25), treatment with zinc picolinate (30 mg, three times daily) for 3 months did not improve subjective taste assessment or taste performance in the entire mouth, although the group receiving zinc picolinate performed significantly better than the placebo group in the filter paper test [202]. However, both the double-blind study by Henkin et al. [171] and the double-blind study in 65 patients by Yoshida et al. [203] failed to confirm this difference. Nevertheless, if the patients with drug-induced taste disturbances were excluded and only the patients with idiopathic taste disturbances and zinc deficiency were analyzed, the result was significant [203].A double-blind study in hemolized patients (n=22) with low zinc levels demonstrated a significant improvement in response to zinc (50 mg/day) given for 12 weeks [204]. Similarly, preliminary findings from a double-blind study with zinc gluconate by Heckmann et al. seemed promising in idiopathic dysgeusia [205], [206].

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Zinc: an Antidepressant by a psychiatrist writing in Psychology Today in 2013, zinc is anti-inflammatory and antidepressant. “Inflammation is the primary driving mechanism behind the whole shebang and may decrease brain zinc levels all on its own.”

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“300 or more enzymes in our bodies use zinc as a buddy to help them do their thing, making DNA, protein synthesis, cell division, all hugely important stuff. Zinc is also critical to cell signaling (a major receptor motif, the “zinc finger” is as famous as the G proteinin cell biology circles). The highest amount of zinc in the body is found in our brains, particularly in a part of our brains called the hippocampus [limbic system]. Zinc deficiency can lead to symptoms of depression, ADHD, difficulties with learning and memory, seizures (2), aggression, and violence (3).”

“…As always, there is a sweet spot of zinc consumption, and more is not always better. More than 50 mg a day can lead to improper copper metabolism, altered iron function, and reduced immune function. We need enough zinc in the right place at the right time…a typical zinc supplement pill of 25-50mg is probably best taken only every few days, unless you are an oyster connoisseur, in which case no supplementation is necessary.” [oysters are highest in zinc]

Abstract

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Incomplete response to monoaminergic antidepressants in major depressive disorder (MDD), and the phenomenon of neuroprogression, suggests a need for additional pathophysiological markers and pharmacological targets. Neuronal zinc is concentrated exclusively within glutamatergic neurons, acting as an allosteric modulator of the N-methyl D-aspartate and other receptors that regulate excitatory neurotransmission and neuroplasticity. Zinc-containing neurons form extensive associational circuitry throughout the cortex, amygdala and hippocampus, which subserve mood regulation and cognitive functions. In animal models of depression, zinc is reduced in these circuits, zinc treatment has antidepressant-like effects and dietary zinc insufficiency induces depressive behaviors. Clinically, serum zinc is lower in MDD, which may constitute a state-marker of illness and a risk factor for treatment-resistance. Marginal zinc deficiency in MDD may relate to multiple putative mechanisms underlying core symptomatology and neuroprogression (e.g. immune dysfunction, monoamine metabolism, stress response dysregulation, oxidative/nitrosative stress, neurotrophic deficits, transcriptional/epigenetic regulation of neural networks). Initial randomized trials suggest a benefit of zinc supplementation. In summary, molecular and animal behavioral data support the clinical significance of zinc in the setting of MDD.

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The material on this site is for informational purposes only.

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It is not legal for me to provide medical advice without an examination.

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It is not a substitute for medical advice, diagnosis or treatment provided by a qualified health care provider.

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Comments are welcome.

This site is not for email, not for medical questions, and not for appointments.

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KPBS Radio highlighted a new study today by UCSD School of Pharmacy

In a new analysispublished Wednesday in the journal Scientific Reports, UC San Diego researchers said millions of FDA side effect records reveal that people who took ketamine for pain relief reported lower rates of depression.

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“The occurrence of complaints about depression dropped in half after ketamine administration,” said UC San Diego Skaggs School of Pharmacy professor Ruben Abagyan, who led the study.

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The researchers focussed on the FDA’s Adverse Effect Reporting System, a database that tracks negative side effects among people who take various drugs. But the researchers were not primarily interested in bad outcomes.

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Instead, they looked for a positive outcome: declining rates of depression among people taking drugs not typically thought of as antidepressants.

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They found signs that other common drugs — including Botox, a pain reliever called diclofenac and the antibiotic minocycline — also reduced depression among patients in the FDA database.

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[minocycline is a glial modulator and it can prevent CRPS from spreading.]

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University of Miami psychiatry professor Charles Nemeroff wrote that the study was, “very interesting.”

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“The findings are of considerable interest. However the interpretation of the findings are key,” he wrote, saying it will be important to understand whether ketamine is directly treating depression or simply relieving pain, which can indirectly help people experience less depression.

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The UC San Diego researchers said they controlled for this variable by comparing people who took ketamine with those who took other pain medications. They said they still found a larger drop in depression among those who took ketamine.

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This is the open source (free) article in Nature with brief excerpts below:

.Isaac V. Cohen, Tigran Makints, Rabia Atayee, Ruben Abagyan

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We found that patients listed in the FAERS database who received ketamine in addition to other therapeutics had significantly lower frequency of reports of depression than patients who took any other combination of drugs for pain (LogOR −0.67 ± 0.034) (Fig. 1c). This reduction in depression is specific to ketamine and is known to be much more rapid than current antidepressants, making this observed effect very promising for treatment of patients with acute depressive or suicidal episodes. These patients cannot afford to wait up to six weeks for reductions in their depressive symptoms. Pain reports were also significantly lower for ketamine patients (LogOR −0.41 ± 0.019) (Fig. 1c).

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The analysis of the whole FAERS database revealed several other unintentional depression reducing drugs among antibiotics, cosmeceuticals and NSAIDS (Fig. 2). Our data supported previous studies that observed the psychiatric polypharmacology of minocycline [my emphasis], a tetracycline antibiotic14 (Fig. 2). The NSAID, diclofenac [that has highest incidence of heart attack and cardiac arrhythmia of any NSAID], was also observed to have some antidepressant properties (Fig. 2). It is theorized that both of these drugs may accomplish antidepressant effects through an anti-inflammatory mechanism. Because of the antidepressant activity of several NSAIDs, we further separated the non-ketamine pain cohort. Ketamine patients were then compared to patients who received any other combination of drugs for pain excluding NSAIDs. It was observed that depression event rates remained low (LogOR −0.56 ± 0.035) (Fig. 2)..The reduction of depression rates in ketamine patient records makes a case for study of ketamine as a psychiatric drug. These results imply that ketamine may be further explored as a monotherapy or adjunct therapy for depression. It should also be noted that FAERS data revealed that ketamine use [may] lead to renal side effects and awareness and caution in patients with renal or hepatic impairment may be warranted (Fig. 1a and b). [my emphasis].

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As an important side note, we also evaluated efficacy and side effects with the use of ketamine for pain management. We found that patients who were on ketamine had reduced opioid induced side effects including constipation (LogOR −0.17 ± 0.023), vomiting (LogOR −0.16 ± 0.025), and nausea (LogOR −0.45 ± 0.034) than patients who received any other combination of drugs for pain indications (Fig. 1d). Our data supports ketamine’s opioid-sparing properties and alludes to the fact that patients may receive benefits of improved pain, reduced requirement of opioids, and ultimately less opioid reduced side effects.

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The results of this study support previous small scale studies’ conclusions that ketamine is a good monotherapy or adjunct therapy for depression. In clinical practice ketamine would be especially useful for depression because of the quick onset of its action compared to existing first line therapies. Regardless of the causative mechanism ketamine appears to have therapeutic potential for TRD. Further, the potential to reduce many of the most complained side effects of opioid treatment makes ketamine adjunct therapy for pain seem desirable.

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Overall, this study demonstrates that the therapeutic potential of ketamine can be derived from appropriate statistical analysis of existing population scale data. This study also outlines a methodology for discovering off label pharmacology of existing approved drugs. This method can be applied to other indications and may reveal new important uses of already approved drugs, providing reliable justification for new indications without large investments in additional clinical trials.

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FDA Adverse Event Reporting System. The FAERS database was created to support FDA’s post marketing surveillance on drugs and biologic therapeutics. It contains adverse reaction and medication error reports sent to the FDA through MedWatch, the FDA Safety Information and Adverse Event Reporting Program. Reporting is voluntary and is done by patients, family members, legal representatives, doctors, pharmacists and other health- care providers. If any party reports an adverse effect to the manufacturer, the manufacturer is legally obligated to forward the report to the FDA. Data is available online in quarterly format for AERS from the first quarter of 2004 to the third quarter of 2012 and for FAERS from the fourth quarter of 2012 to the first quarter of 2016.

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The study used over 8 million adverse event reports from first quarter of 2004 to the first quarter of 2016. All the quarterly files from 2004 to 2016 were combined into a master file which was used as the primary source for analysis. . . .

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Out of 8 million reports, 279,853 reports were used for analysis of ketamine in Fig. 1. Two cohorts for ketamine (K) patients and pain (P) patients with 41,337 and 238,516 patients respectively....

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The material on this site is for informational purposes only.

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It is not legal for me to provide medical advice without an examination.

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It is not a substitute for medical advice, diagnosis or treatment provided by a qualified health care provider.